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CNS10-NPC-GDNF for the Treatment of ALS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02943850
Recruitment Status : Active, not recruiting
First Posted : October 25, 2016
Last Update Posted : October 11, 2018
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Robert H. Baloh, Cedars-Sinai Medical Center

Tracking Information
First Submitted Date  ICMJE October 20, 2016
First Posted Date  ICMJE October 25, 2016
Last Update Posted Date October 11, 2018
Actual Study Start Date  ICMJE April 1, 2017
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
Safety evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments [ Time Frame: Patients will be followed postoperatively for 12 months ]
Safety, as evaluated by:
  • Adverse Events and Serious Adverse Events
  • Post-op MRI
  • Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02943850 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
  • Compound Motor Action Potential (CMAP) [ Time Frame: CMAP will be performed 7 times over 15 months ]
    Compound Motor Action Potential - CMAP (Tibialis anterior)
  • Force Generation via ATLIS testing [ Time Frame: ATLIS testing will be performed 7 times over 15 months ]
    Lower extremity Force Generation via ATLIS testing
  • Quantitative Muscle MRI [ Time Frame: Muscle MRI will be performed 6 times over 15 months ]
    Quantitative Muscle MRI of bilateral lower extremities
  • Electrical Impedance Myography (EIM) [ Time Frame: EIM will be performed 7 times over 15 months ]
    Lower Extremity Electrical Impedance Myography (EIM)
  • Assessment of glial cell line derived neurotrophic factor (GDNF) in the cerebral spianl fluid (CSF) [ Time Frame: CSF will be collected at 3 time points over 12 months ]
    Assessment of GDNF in the CSF
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CNS10-NPC-GDNF for the Treatment of ALS
Official Title  ICMJE Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) for the Treatment of Amyotrophic Lateral Sclerosis
Brief Summary The investigator is examining the safety of transplanting cells that have been engineered to produce a growth factor into the spinal cord of patients with Amyotrophic Lateral Sclerosis (ALS). The cells are called neural progenitor cells, which are a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, which is a type of neuronal cell. The growth factor is called glial cell line-derived neurotrophic factor, or GDNF. GDNF is a protein that promotes the survival of many types of neuronal cells. Therefore, the cells are called "CNS10-NPC-GDNF." The investigational treatment has been tested in animals, but it has not yet been tested in people. In this study, we want to learn if CNS10-NPC-GDNF cells are safe to transplant into the spinal cords of people.
Detailed Description

This study will be the first to use a genetically modified progenitor cells to treat a neurodegenerative disease. This is a Phase 1/2a, single-center, blinded (as to side of injection), safety study of two escalating doses of human neural progenitor cells expressing GDNF (CNS10-NPC-GDNF) delivered unilaterally to the lumbar region in ALS subjects with moderate leg involvement.

Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups. Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least two weeks between surgeries.

Specific aims:

Safety, as evaluated by:

  • Adverse Events and Serious Adverse Events
  • Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Biological: Stem cell (HPC) implantation
    All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.
  • Device: Stereotactic surgical device
    A newly developed stereotactic frame is being evaluated as a part of this trial
Study Arms  ICMJE Experimental: Stem cell implantation
Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups (Group A and B). Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least one week between surgeries. There will be 9 subjects in each group. No control group is included. All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.
Interventions:
  • Biological: Stem cell (HPC) implantation
  • Device: Stereotactic surgical device
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2016)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)
  2. Duration of symptoms ≤ 36 months
  3. Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.
  4. Forced Vital Capacity >60% of predicted normal in supine.
  5. Male/Female; Age: 18 and older
  6. Able to provide Informed Consent
  7. Be geographically accessible to the study site and able to travel to study site for required visits
  8. Have caregiver to assist in the transportation and care required by participation in the study
  9. Not taking riluzole or on a stable dose for ≥ 30 days
  10. For women of child bearing capacity, negative pregnancy test prior to surgery
  11. Medically able to undergo thoracolumbar laminectomy or laminoplasty as determined by the site PI and Neurosurgeon
  12. Medically able to tolerate the immunosuppression regimen as determined by the site PI

Exclusion Criteria:

  1. Using invasive ventilatory assistance
  2. Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
  3. Presence of any of the following conditions:

    1. Current drug or alcohol abuse
    2. Any known immunodeficiency syndrome
    3. Unstable medical condition
    4. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
  4. Persons of child bearing capacity not willing to practice birth control
  5. Receiving any investigational device/biologic/drug in past 30 days or any previous exposure to stem cell therapy
  6. Any condition in the lower extremities which precludes serial strength testing
  7. Any condition that the Neurosurgeon feels may pose complications for the surgery
  8. Any condition or ALS disease phenotype that the site PI feels may interfere with participation in the study or in the interpretation of study endpoints
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02943850
Other Study ID Numbers  ICMJE Pro00042350
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Robert H. Baloh, Cedars-Sinai Medical Center
Study Sponsor  ICMJE Cedars-Sinai Medical Center
Collaborators  ICMJE California Institute for Regenerative Medicine (CIRM)
Investigators  ICMJE
Principal Investigator: Robert H. Baloh, MD, PhD Cedars-Sinai Medical Center
PRS Account Cedars-Sinai Medical Center
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP